Primary Aldosteronism: A Glimpse into the Most Common Endocrine Cause of Arterial Hypertension

Compelling evidences showed that primary aldosteronism (PA) is a quite common disease. In spite of this, hypertensive patients are seldom screened for PA and, therefore, many patients are mislabelled as (low-renin) essential hypertension thereby remaining exposed to the nefarious consequences of long-term hyperaldosteronism. In this chapter we reviewed the clinical aspects of PA and the evidences supporting the need of implementing strategies aimed at diagnosing early PA patients. After reporting the prevalence rates of PA in different cohorts of hypertensive patients, we examined the reasons why PA is rarely searched for. The cardiovascular and renal damage associated with PA were also discussed, with particular emphasis to endothelial dysfunction, vascular remodeling, left ventricular changes, fibrosis, diastolic dysfunction, atrial fibrillation and chronic kidney disease. Studies supporting the concept that PA-associated organ damage can be prevented and even regressed with a timely diagnosis were also reviewed. A flowchart illustrating the proposal of a simplified diagnostic algorithm for screening and subtyping of PA, which allows circumventing the complexity of a diagnostic workup centred on confirmatory tests, is also proposed. Finally, the principles of treatment for PA are discussed

Chromogranin a measurement for assessing the selectivity of adrenal venous sampling in primary aldosteronism.

The assessment of selectivity of blood sampling is a fundamental step for a proper interpretation of the results of adrenal vein sampling (AVS), which is a "must" for identifying the surgically curable subtypes of primary aldosteronism. However, uncertainties remain on how to best achieve this goal

Urotensin II Exerts Pressor Effects by Stimulating Renin and Aldosterone Synthase Gene Expression

Abstract We investigated the in vivo pressor effects of the potent vasoconstrictor Urotensin II (UII). We randomized normotensive Sprague-Dawley rats into 4 groups that received a 7-day UII infusion (cases) or vehicle (controls). Group 1 received normal sodium intake; Group 2 underwent unilateral nephrectomy and salt loading; Group 3 received spironolactone, besides unilateral nephrectomy and salt loading; Group 4 only received spironolactone. UII raised BP transiently after a lag phase of 12-36 hours in Group 1, and progressively over the week in Group 2. Spironolactone did not affect blood pressure, but abolished both pressor effects of UII in Group 3, and left blood pressure unaffected in Group 4. UII increased by 7-fold the renal expression of renin in Group 2, increased aldosterone synthase expression in the adrenocortical zona glomerulosa, and prevented the blunting of renin expression induced by high salt. UII raises BP transiently when sodium intake and renal function are normal, but progressively in salt-loaded uninephrectomized rats. Moreover, it increases aldosterone synthase and counteracts the suppression of renin induced by salt loading. This novel action of UII in the regulation of renin and aldosterone synthesis could play a role in several clinical conditions where UII levels are up-regulated

Endothelial Factors in The Pathogenesis and Treatment of Chronic Kidney Disease Part II: Role in Disease Conditions. A Joint Consensus Statement from the ESH Working Group on Endothelin and Endothelial Factors And The Japanese Society of Hypertension

: After examining in Part I the general mechanisms of endothelial cell injury in the kidney, the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension and the Japanese Society of Hypertension will herein review current knowledge on the role of endothelial dysfunction in multiple disease conditions that affect the kidney, including diabetes mellitus, preeclampsia, solid organ transplantation, hyperhomocysteinemia and antiangiogenic therapy in cancer. The few available randomized controlled clinical trials specifically designed to evaluate strategies for correcting endothelial dysfunction in patients with hypertension and/or chronic kidney disease are also discussed alongside their cardiovascular and renal outcomes

Exhaled and arterial levels of endothelin-1 are increased and correlate with pulmonary systolic pressure in COPD with pulmonary hypertension

BACKGROUND: Endothelin-1 (ET-1) and Nitric Oxide (NO) are crucial mediators for establishing pulmonary artery hypertension (PAH). We tested the hypothesis that their imbalance might also occur in COPD patients with PAH. METHODS: The aims of the study were to measure exhaled breath condensate (EBC) and circulating levels of ET-1, as well as exhaled NO (FENO) levels by, respectively, a specific enzyme immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD with PAH (12), COPD only (36), and healthy individuals (15). In order to evaluate pulmonary-artery systolic pressure (PaPs), all COPD patients underwent Echo-Doppler assessment. RESULTS: Significantly increased exhaled and circulating levels of ET-1 were found in COPD with PAH compared to both COPD (p < 0.0001) only, and healthy controls (p < 0.0001). In COPD with PAH, linear regression analysis showed good correlation between ET-1 in EBC and PaPs (r = 0.621; p = 0.031), and between arterial levels of ET-1 and PaPs (r = 0.648; p = 0.022), while arterial levels of ET-1 inversely correlated with FEV1%, (r = -0.59, p = 0.043), and PaPs negatively correlated to PaO2 (r = -0.618; p = 0.032). Significantly reduced levels of FENO were found in COPD associated with PAH, compared to COPD only (22.92 +/- 11.38 vs.35.07 +/- 17.53 ppb; p = 0.03). Thus, we observed an imbalanced output in the breath between ET-1 and NO, as expression of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to COPD only. Whether this imbalance is an early cause or result of PAH due to COPD is still unknown and deserves further investigations

High sodium intake, glomerular hyperfiltration and protein catabolism in patients with essential hypertension

Aims: A blood pressure-independent metabolic shift toward a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures, as surrogates for cardiovascular risk, in hypertensive patients. Methods and results: We analysed clinical and biochemical data from 766 consecutive patients with essential hypertension, collected at the time of screening for secondary causes. The systematic screening protocol included 24h urine collection on usual diet and avoidance of renin-angiotensin-aldosterone system-confounding medications. Urinary 24h-Na+ excretion, used to define classes of Na+ intake (Low ≤2.3g/d; Medium 2.3-5g/d; High &gt;5g/d), was an independent predictor of glomerular filtration rate after correction for age, sex, blood pressure, BMI, aldosterone and potassium excretion (p = 0.001; Low: 94.1 [69.9-118.8] vs High: 127.5 [108.3-147.8] ml/min/1.73m2). Renal Na+ and water handling diverged, with higher fractional excretion of Na+ and lower fractional excretion of water in those with evidence of High Na+ intake (FENa: Low 0.39% [0.30-0.47] vs. High 0.81% [0.73-0.98], p &lt; 0.001; FEwater: Low 1.13% [0.73-1.72] vs. High 0.89% [0.69-1.12], p = 0.015). Despite higher FENa, these patients showed higher absolute 24h Na+ reabsorption and higher associated tubular energy expenditure, estimated by tubular Na+/ATP stoichiometry, accordingly (ΔHigh-Low = 18 [12-24] kcal/d, p &lt; 0.001). At non-targeted LC/MS plasma metabolomics in an unselected subcohort (n = 67), metabolites which were more abundant in High vs. Low Na+ intake (p &lt; 0.05) mostly entailed intermediates or end products of protein catabolism/urea cycle. Conclusions: When exposed to high Na+ intake, kidneys dissociate Na+ and water handling. In hypertensive patients, this comes at the cost of higher glomerular filtration rate, increased tubular energy expenditure and protein catabolism from endogenous (muscle) or excess exogenous (dietary) sources. Glomerular hyperfiltration and the metabolic shift may have broad implications on global cardiovascular risk independent of blood pressure

Is exercise becoming a danger for our health? The complex relationship between exercise and atrial fibrillation

Invited Editoria